While the patterns of drug metabolism and disposition characteristic of the adult are not expressed until puberty, they are most probably determined during critical developmental periods. Furthermore, developmental organizers for adult patterns of drug metabolism and actions can permanently alter the genetic regulation of pharmacological responses. Once established, this imprinting is permanent and irreversible, although transient changes can be produced by environmental (i.e., drugs, nutrition) or internal influences (i.e., diseases, hormones). By measuring hepatic drug metabolic enzymes, barbiturate induced sleeping times, drug clearance rates and drug receptor levels in the brains of animals with experimentally induced and genetic defects in the imprinting of drug metabolism, we plan to identify the critical periods and developmental determinants that organize the differentiating liver and brain for the subsequent appearance of adult patterns of drug metabolism and disposition.